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1.
Identification of specialized pro-resolving mediator clusters from healthy adults after intravenous low-dose endotoxin and omega-3 supplementation: a methodological validation.
Norris, PC, Skulas-Ray, AC, Riley, I, Richter, CK, Kris-Etherton, PM, Jensen, GL, Serhan, CN, Maddipati, KR
Scientific reports. 2018;(1):18050
Abstract
Specialized pro-resolving mediator(s) (SPMs) are produced from the endogenous ω-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and accelerate resolution of acute inflammation. We identified specific clusters of SPM in human plasma and serum using LC-MS/MS based lipid mediator (LM) metabololipidomics in two separate laboratories for inter-laboratory validation. The human plasma cluster consisted of resolvin (Rv)E1, RvD1, lipoxin (LX)B4, 18-HEPE, and 17-HDHA, and the human serum cluster consisted of RvE1, RvD1, AT-LXA4, 18-HEPE, and 17-HDHA. Human plasma and serum SPM clusters were increased after ω-3 supplementation (triglyceride dietary supplements or prescription ethyl esters) and low dose intravenous lipopolysaccharide (LPS) challenge. These results were corroborated by parallel determinations with the same coded samples in a second, separate laboratory using essentially identical metabololipidomic operational parameters. In these healthy subjects, two ω-3 supplementation protocols (Study A and Study B) temporally increased the SPM cluster throughout the endotoxin-challenge time course. Study A and Study B were randomized and Study B also had a crossover design with placebo and endotoxin challenge. Endotoxin challenge temporally regulated lipid mediator production in human serum, where pro-inflammatory eicosanoid (prostaglandins and thromboxane) concentrations peaked by 8 hours post-endotoxin and SPMs such as resolvins and lipoxins initially decreased by 2 h and were then elevated at 24 hours. In healthy adults given ω-3 supplementation, the plasma concentration of the SPM cluster (RvE1, RvD1, LXB4, 18-HEPE, and 17-HDHA) peaked at two hours post endotoxin challenge. These results from two separate laboratories with the same samples provide evidence for temporal production of specific pro-resolving mediators with ω-3 supplementation that together support the role of SPM in vivo in inflammation-resolution in humans.
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2.
Metabolomics approach by 1H NMR spectroscopy of serum reveals progression axes for asymptomatic hyperuricemia and gout.
Zhang, Y, Zhang, H, Chang, D, Guo, F, Pan, H, Yang, Y
Arthritis research & therapy. 2018;(1):111
Abstract
BACKGROUND Gout is a metabolic disease and is the most common form of inflammatory arthritis affecting men. However, the pathogenesis of gout is still uncertain, and novel biomarkers are needed for early prediction and diagnosis of gout. The aim of this study was to develop a systemic metabolic profile of patients with asymptomatic hyperuricemia (HUA) and gout by using a metabolomics approach, and find potential pathophysiological mechanisms of and markers of predisposition to gout. METHODS Serum samples were collected from 149 subjects, including 50 patients with HUA, 49 patients with gout and 50 healthy controls. 1H nuclear magnetic resonance (NMR) spectroscopy combined with principal components analysis and orthogonal partial least squares-discriminant analysis were used to distinguish between samples from patients and healthy controls. Clinical measurements and pathway analysis were also performed to contribute to understanding of the metabolic change. RESULTS By serum metabolic profiling, 21 metabolites including lipids and amino acids were significantly altered in patients with HUA or gout. The levels of identified biomarkers together with clinical data showed apparent alteration trends in patients with HUA or gout compared to healthy individuals. According to pathway analysis, three and five metabolic pathways were remarkably perturbed in patients with HUA or gout, respectively. These enriched pathways involve in lipid metabolism, carbohydrate metabolism, amino acids metabolism and energy metabolism. CONCLUSIONS Taken together, we identified the biomarker signature for HUA and gout, which provides biochemical insights into the metabolic alteration, and identified a continuous progressive axis of development from HUA to gout.
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3.
Current trends to comprehend lipid metabolism in diatoms.
Zulu, NN, Zienkiewicz, K, Vollheyde, K, Feussner, I
Progress in lipid research. 2018;:1-16
Abstract
Diatoms are the most dominant phytoplankton species in oceans and they continue to receive a great deal of attention because of their significant contributions in ecosystems and the environment. Due to triacylglycerol (TAG) profiles that are abundant in medium-chain fatty acids, diatoms have emerged to be better feed stocks for biofuel production, in comparison to the commonly studied green microalgal species (chlorophytes). Importantly, diatoms are also known for their high levels of the essential ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are considered to be a promising alternative source of these components. The two most commonly exploited diatoms include Thalassiosira pseudonana and Phaeodactylum tricornutum. Although obvious similarities between diatoms and chlorophytes exist, there are some substantial differences in their lipid metabolism. This review provides an overview on lipid metabolism in diatoms, with P. tricornutum as the most explored model. Special emphasis is placed on the synthesis and incorporation of very long chain ω3 fatty acids into lipids. Furthermore, current approaches including genetic engineering and biotechnological methods aimed at improving and maximizing lipid production in P. tricornutum are also discussed.
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4.
The implication of diabetes metabolomics in the early diagnosis and pathogenesis of pancreatic cancer.
Lou, YB, Fan, FX, Mu, YC, Dong, X
Journal of biological regulators and homeostatic agents. 2018;(1):75-82
Abstract
The aim of this study was to analyze metabolite differences in pancreatic cancer and diabetic patients, to better diagnose these diseases. Gas chromatography-mass spectrometry was used to evaluate the metabolomic differences in blood samples of 50 pancreatic patients, 50 diabetic patients and 50 healthy people. Metabonomic data was analyzed with primary component analysis and discriminant analysis. The results show that pancreatic cancer patients, diabetic patients and healthy people can have significantly distinct metabolite profiles. Upregulated metabolites in the serum of the diabetic group included sugars (glucose, fructose), cholesterol, tyrosine and phosphoric acid and other substances, and down-regulation was observed in lactic acid, glycine, alanine, glutamine, proline, citric acid and other substances. It is indicated that identification of the most common changes in specific markers between the two diseases, can provide a new perspective and experimental basis for a better understanding of the metabolic differences and the pathogenesis of the two diseases in future. The present study sheds new light on the diagnosis of pancreatic cancer and diabetes.
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5.
Metabolomic profiling of women with gestational diabetes mellitus and their offspring: Review of metabolomics studies.
Chen, Q, Francis, E, Hu, G, Chen, L
Journal of diabetes and its complications. 2018;(5):512-523
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) reflects an increased risk of developing type 2 diabetes (T2D) after pregnancy in women. Offspring born to mothers with GDM are at an elevated risk of obesity and T2D at a young age. Currently, there are lack of ways for identifying women in early pregnancy who are at risk of developing GDM. As a result, both mothers and fetus are not treated until late in the second trimester when GDM is diagnosed. The recent advance in metabolomics, a new approach of systematic investigation of the metabolites, provides an opportunity for early detection of GDM, and classifying the risk of subsequent chronic diseases among women and their offspring. METHODS We reviewed the literatures published in the past 20 years on studies using high-throughput metabolomics technologies to investigate women with GDM and their offspring. CONCLUSIONS Despite the inconsistent results, previous studies have identified biomarkers that involved in specific metabolite groups and several pathways, including amino acid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, and fatty acid metabolism. However, most studies have small sample sizes. Further research is warranted to determine if metabolomics will result in new indicators for the diagnosis, management, and prognosis of GDM and related complications.
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6.
Discovery and Validation of Potential Serum Biomarkers for Pediatric Patients with Congenital Heart Diseases by Metabolomics.
Yu, M, Sun, S, Yu, J, Du, F, Zhang, S, Yang, W, Xiao, J, Xie, B
Journal of proteome research. 2018;(10):3517-3525
Abstract
To identify and screen serum biomarkers to determine pediatric patients with congenital heart diseases (PCH) from healthy control children (NC), a total of 614 clinically diagnosed subjects from three hospitals, including 491 PCH and 234 NC, were enrolled for nontargeted proton nuclear magnetic resonance spectroscopy (1H NMR)-based and targeted ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. Nineteen serum metabolites distinguishing PCH from NC were identified by 1H NMR-based metabolomic analysis. The amino acid and choline metabolic pathways were considered to be closely related to PCH. The serum levels of 13 metabolites in these two pathways were further determined by UPLC-MS/MS and observed to be altered significantly in PCH. Taurine, glutamine, and glutamate presented considerable diagnostic value for the diagnosis of PCH (AUROC > 0.80). Logistic regression analysis showed that a combination of four variables, namely, betaine, taurine, glutamine, and phenylalanine, yields a high diagnostic value (AUROC = 0.949) and prediction accuracy (89.1%) for differentiating PCH from the NC, and the sensitivity and specificity were 93.9 and 95.2%, respectively. Further double-blind sample prediction showed that the accuracy of the model was 83.8% for 80 unknown samples. Our results showed that the serum amino acid and choline metabolite levels in PCH were changed considerably. The combination of four metabolites, namely, betaine, taurine, glutamine, and phenylalanine, can be used as potential serum biomarkers in PCH diagnosis, which contributes to the early PCH screening.
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7.
Metabolome analysis of esophageal cancer tissues using capillary electrophoresis-time-of-flight mass spectrometry.
Tokunaga, M, Kami, K, Ozawa, S, Oguma, J, Kazuno, A, Miyachi, H, Ohashi, Y, Kusuhara, M, Terashima, M
International journal of oncology. 2018;(6):1947-1958
Abstract
Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgically excised pair-wise from 35 patients with esophageal cancer. Following tissue homogenization and metabolite extraction, a total of 110 compounds were absolutely quantified by CE-TOFMS. We compared the concentrations of the metabolites between Ts and NTs, between pT1 or pT2 (pT1-2) and pT3 or pT4 (pT3-4) stage, and between node-negative (pN-) and node-positive (pN+) samples. Principal component analysis and hierarchical clustering analysis revealed clear metabolomic differences between Ts and NTs. Lactate and citrate levels in Ts were significantly higher (P=0.001) and lower (P<0.001), respectively, than those in NTs, which corroborated with the Warburg effect in Ts. The concentrations of most amino acids apart from glutamine were higher in Ts than in NTs, presumably due to hyperactive glutaminolysis in Ts. The concentrations of malic acid (P=0.015) and citric acid (P=0.008) were significantly lower in pT3-4 than in pT1-2, suggesting the downregulation of tricarboxylic acid (TCA) cycle activity in pT3-4. On the whole, in this study, we demonstrate significantly different metabolomic characteristics between tumor and non-tumor tissues and identified a novel set of metabolites that were strongly associated with the degree of tumor progression. A further understanding of cancer metabolomics may enable the selection of more appropriate treatment strategies, thereby contributing to individualized medicine.
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8.
Contribution of Untargeted Metabolomics for Future Assessment of Biotech Crops.
Christ, B, Pluskal, T, Aubry, S, Weng, JK
Trends in plant science. 2018;(12):1047-1056
Abstract
The nutritional value and safety of food crops are ultimately determined by their chemical composition. Recent developments in the field of metabolomics have made it possible to characterize the metabolic profile of crops in a comprehensive and high-throughput manner. Here, we propose that state-of-the-art untargeted metabolomics technology should be leveraged for safety assessment of new crop products. We suggest generally applicable experimental design principles that facilitate the efficient and rigorous identification of both intended and unintended metabolic alterations associated with a newly engineered trait. Our proposition could contribute to increased transparency of the safety assessment process for new biotech crops.
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9.
A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.
Michelini, S, Balakrishnan, B, Parolo, S, Matone, A, Mullaney, JA, Young, W, Gasser, O, Wall, C, Priami, C, Lombardo, R, et al
Microbiome. 2018;(1):171
Abstract
BACKGROUND Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space. RESULTS Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial ( http://www.nourishtoflourish.auckland.ac.nz/ ). CONCLUSIONS In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.
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10.
Metabolomic profiling implicates adiponectin as mediator of a favorable lipoprotein profile associated with NT-proBNP.
Masuch, A, Pietzner, M, Bahls, M, Budde, K, Kastenmüller, G, Zylla, S, Artati, A, Adamski, J, Völzke, H, Dörr, M, et al
Cardiovascular diabetology. 2018;(1):120
Abstract
BACKGROUND The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach. METHODS Lipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine. RESULTS An increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles. CONCLUSIONS Most of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.